Among people living with HIV (PLWH), there is a 50% increased risk of acute myocardial infection compared to the general population. Although the advent of highly active antiretroviral therapy (HAART) has had several benefits for PLWH,including increased life expectancy, the longer life span has also made this population apt to develop comorbidities seen in age-matched individuals without HIV, including cardiovascular disease. In addition, HAART itself is a risk factor for cardiovascular disease (CVD), and persistent inflammation and chronic immune activation caused by HIV and ART results in a proinflammatory state that also increases the risk for cardiovascular disease. Hepatitis C (HCV) is another chronic viral infection with significant morbidity and mortality. The development of directly acting antivirals (DAAs) has dramatically improved the cure rate of HCV treatment. However, besides the effects on the liver, chronic infection with HCV leads to numerous extrahepatic manifestations that are associated with morbidity and mortality, including cardiovascular disease. Therefore, patients co-infected with HCV and HIV have a magnified cardiovascular risk than that of the general population. If treatment of HCV can lower the risk of CVD among HIV and HCV co-infected patients, then this would provide an indication for early HCV treatment in this population. As such, we are initiating a pilot, intervention, non-randomized, controlled prospective study to treat HCV in mono-infected and HIV co-infected individuals and compare cardiovascular risk outcomes to HIV mono-infected controls. This pilot study will demonstrate whether functional cure of HCV reduces myocardial injury and risk of cardiovascular disease. The proposal was funded by the Bench-to-Bedside program at NIH and the IHV ID Department and Merck. The MRIs will be done at the NIH. The IRB of Record will be the University of Maryland Baltimore. The protocol has enrolled 22 patients and should complete enrollment in 2020.